TY - JOUR
T1 - A neurobiological pathway to smoking in adolescence
T2 - TTC12-ANKK1-DRD2 variants and reward response
AU - IMAGEN Consortium
AU - Macare, Christine
AU - Ducci, Francesca
AU - Zhang, Yuning
AU - Ruggeri, Barbara
AU - Jia, Tianye
AU - Kaakinen, Marika
AU - Kalsi, Gursharan
AU - Charoen, Pimphen
AU - Casoni, Filippo
AU - Peters, Jan
AU - Bromberg, Uli
AU - Hill, Matthew
AU - Buxton, Jessica
AU - Blakemore, Alexandra
AU - Veijola, Juha
AU - Büchel, Christian
AU - Banaschewski, Tobias
AU - Bokde, Arun L W
AU - Conrod, Patricia
AU - Flor, Herta
AU - Frouin, Vincent
AU - Gallinat, Jürgen
AU - Garavan, Hugh
AU - Gowland, Penny A
AU - Heinz, Andreas
AU - Ittermann, Bernd
AU - Lathrop, Mark
AU - Martinot, Jean-Luc
AU - Paus, Tomáš
AU - Desrivières, Sylvane
AU - Munafò, Marcus
AU - Järvelin, Marjo-Riitta
AU - Schumann, Gunter
N1 - Copyright © 2018. Published by Elsevier B.V.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - The TTC12-ANKK1-DRD2 gene-cluster has been implicated in adult smoking. Here, we investigated the contribution of individual genes in the TTC12-ANKK1-DRD2 cluster in smoking and their association with smoking-associated reward processing in adolescence. A meta-analysis of TTC12-ANKK1-DRD2 variants and self-reported smoking behaviours was performed in four European adolescent cohorts (N = 14,084). The minor G-allele of rs2236709, mapping TTC12, was associated with self-reported smoking (p = 5.0 × 10−4) and higher plasma cotinine levels (p = 7.0 × 10−5). This risk allele was linked to an increased ventral-striatal blood-oxygen level-dependent (BOLD) response during reward anticipation (n = 1,263) and with higher DRD2 gene expression in the striatum (p = 0.013), but not with TTC12 or ANKK gene expression. These data suggest a role for the TTC12-ANKK1-DRD2 gene-cluster in adolescent smoking behaviours, provide evidence for the involvement of DRD2 in the early stages of addiction and support the notion that genetically-driven inter-individual differences in dopaminergic transmission mediate reward sensitivity and risk to smoking.
AB - The TTC12-ANKK1-DRD2 gene-cluster has been implicated in adult smoking. Here, we investigated the contribution of individual genes in the TTC12-ANKK1-DRD2 cluster in smoking and their association with smoking-associated reward processing in adolescence. A meta-analysis of TTC12-ANKK1-DRD2 variants and self-reported smoking behaviours was performed in four European adolescent cohorts (N = 14,084). The minor G-allele of rs2236709, mapping TTC12, was associated with self-reported smoking (p = 5.0 × 10−4) and higher plasma cotinine levels (p = 7.0 × 10−5). This risk allele was linked to an increased ventral-striatal blood-oxygen level-dependent (BOLD) response during reward anticipation (n = 1,263) and with higher DRD2 gene expression in the striatum (p = 0.013), but not with TTC12 or ANKK gene expression. These data suggest a role for the TTC12-ANKK1-DRD2 gene-cluster in adolescent smoking behaviours, provide evidence for the involvement of DRD2 in the early stages of addiction and support the notion that genetically-driven inter-individual differences in dopaminergic transmission mediate reward sensitivity and risk to smoking.
U2 - 10.1016/j.euroneuro.2018.07.101
DO - 10.1016/j.euroneuro.2018.07.101
M3 - Article (Academic Journal)
C2 - 30104163
SN - 0924-977X
VL - 28
SP - 1103
EP - 1114
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
IS - 10
ER -